The U.S. Food and Drug Administration today granted accelerated approval to Vyondys 53 (golodirsen) injection to treat Duchenne muscular dystrophy (DMD) patients who have a confirmed mutation of the dystrophin gene that is amenable to exon 53 skipping. It is estimated that about 8 percent of patients with DMD have this mutation. "The FDA recognizes the urgent need for new medical treatments for serious neurological disorders and we have a long-standing commitment to working with researchers, drug companies and patients to facilitate the development and approval of treatments for rare diseases. With today's accelerated approval, patients with Duchenne - a rare and devastating disease - who have a confirmed mutation of the dystrophin gene amenable to exon 53 skipping will now have available the first treatment targeted specifically for this disease subtype," said Billy Dunn, M.D., acting director of the Office of Neuroscience in the FDA's Center for Drug Evaluation and Research. "Use of the accelerated approval pathway will make Vyondys 53 available to patients based on initial data and we look forward to learning more about the drug's clinical benefit from the ongoing confirmatory clinical trial." DMD is a rare genetic disorder characterized by progressive muscle deterioration and weakness. It is the most common type of muscular dystrophy. DMD is caused by an absence of dystrophin, a protein that helps keep muscle cells intact. The first symptoms are usually seen between three and five years of age and worsen over time. The disease often occurs in people without a known family history of the condition and primarily affects boys, but in rare cases it can affect girls. DMD occurs in about one out of every 3,600 male infants worldwide. People with DMD progressively lose the ability to perform activities independently and often require a wheelchair by their early teens. As the disease progresses, life-threatening heart and respiratory conditions can occur. Patients typically succumb to the disease in their 20s or 30s; however, disease severity and life expectancy vary. Vyondys 53 was approved under the accelerated approval pathway, which provides for the approval of drugs that treat serious or life-threatening diseases and generally offer a meaningful advantage over existing treatments. Approval under this pathway can be based on adequate and well-controlled studies showing the drug has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit to patients (i.e., how patients feel or function or whether they survive). This pathway provides earlier patient access to promising new drugs while the company conducts clinical trials to verify the predicted clinical benefit. The accelerated approval of Vyondys 53 is based on the surrogate endpoint of an increase in dystrophin production in the skeletal muscle observed in some patients treated with the drug. The FDA has concluded that the data submitted by the applicant demonstrated an increase in dystrophin production that is reasonably likely to predict clinical benefit in patients with DMD who have a confirmed mutation of the dystrophin gene amenable to exon 53 skipping. A clinical benefit of the drug, including improved motor function, has not been established. In making this decision, the FDA considered the potential risks associated with the drug, the life-threatening and debilitating nature of the disease and the lack of available therapy. Vyondys 53 was evaluated in a two-part clinical study. The first part included 12 DMD patients, with eight patients receiving Vyondys 53 and four receiving placebo. The second part of the study was open-label, and included the 12 patients enrolled in part one of the study, and 13 additional patients who had not previously received the treatment. In the study, dystrophin levels increased, on average, from 0.10% of normal at baseline to 1.02% of normal after 48 weeks of treatment with the drug or longer. As part of the accelerated approval process, the FDA is requiring the company to conduct a clinical trial to confirm the drug’s clinical benefit. The ongoing study is designed to assess whether Vyondys 53 improves motor function of DMD patients with a confirmed mutation of the dystrophin gene amenable to exon 53 skipping. If the trial fails to verify clinical benefit, the FDA may initiate proceedings to withdraw approval of the drug. The most common side effects reported by participants receiving Vyondys 53 in clinical studies were headache, fever (pyrexia), cough, vomiting, abdominal pain, cold symptoms (nasopharyngitis) and nausea. Hypersensitivity reactions, including rash, fever, itching, hives, skin irritation (dermatitis) and skin peeling (exfoliation), have occurred in patients who were treated with Vyondys 53. Additionally, renal toxicity was observed in animals who received golodirsen. Although renal toxicity was not observed in the clinical studies with Vyondys 53, renal toxicity, including potentially fatal glomerulonephritis, has been observed after administration of some antisense oligonucleotides. Renal function should be monitored in patients taking Vyondys 53. The FDA granted this application Fast Track and Priority Review designations. Vyondys 53 also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases. In addition, the manufacturer received a rare pediatric disease priority review voucher. The FDA's rare pediatric disease priority review voucher program is intended to encourage development of new drugs and biologics to prevent and treat rare diseases in children. Approval of Vyondys 53 was granted to Sarepta Therapeutics of Cambridge, Massachusetts.